CHEMOTHERAPY Introduction 1

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CHEMOTHERAPY

Introduction

By Firewoin B.

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Objective

At the end of this lesson the trainee will be

able understand:-

The definition of some terminology inchemotherapy.

Principle of antimicrobial therapy

Problems that arise with the use of antimicrobials

Classification of chemotherapeutic agents.

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INTRODUCTION

The term chemotherapy was coined by Ehrlich

at the beginning of the century to describe the

use of synthetic chemicals to destroy infective

agents.

Now refers more broadly to the use of any

chemical compound that selectively acts on

microbes or cancer.

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INTRODUCTION (CONT.)

Antibiotics are substances produced byvarious species of M.O (bacteria, fungi, andactinomycetes) that suppress the growth ofother M.O. at low con.

Antimicrobial agents (AMAs) is generalizedone to designate synthetic as well as naturallyobtained drugs that attenuate M.O.

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AMAs differ markedly in;- Physical properties,

Chemical properties,

Pharmacological properties,

Antimicrobial spectra, and

Mechanisms of action. Knowledge of molecular mechanisms of

bacterial replication has greatly facilitatedrational development of cpds that caninterfere with their replication.

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Antimicrobial agents are among the mostdramatic examples of the advances ofmodern medicine.

Many infectious diseases once consideredincurable and lethal are now amenable totreatment with a few pills.

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The remarkable specific activity of AMAs isdue to their selectivity for targets that areeither unique to MO or much more importantin them than in humans.

Among these targets are:- Bacterial and fungal cell wall-synthesizing enzymes,

The bacterial ribosome , the enzymesrequired for nucleotide synthesis and

DNA replication, and The machinery of viral replication.

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Sources of antimicrobial1. Microbial

Penicillin,Streptomaycin,

Chloramphenicol

2. Semisynthetic

Oral penicillin

3. Synthetic

INH, Sulphonamides, Qunolons

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Problems that arise with the use of

antimicrobials

1. Toxicity

1. Local irritation

At the site of administration

GI irritation Pain and abscess formation at the site of Im

injection

Thrombophlebitis of the injected vein

2.

Systemic toxicity Practically all AMAs produces dose related

and predictable organ toxicity.

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antimicrobials (Cont.)

2. Hypersensitivity reaction

It is unpredictable and unrelated to dose

The whole rang of reaction from rash-

Anaphylactic shock can be produced.3. Drug resistance

It refers to unresponsiveness of a m.o to

AMAs and is kin to the phenomena of

tolerance seen in higher organisms.

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Type of resistance

Natural resistance

Some microbial have always been resistance

to certain AMAs. They lack the metabolic process or the target site

which is affected by the particular drugs.

It is generally a group or speciescharacteristic.

Gram -ve bacilli are normally unaffected bypencillin G.

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Acquired resistance

It is the development of resistance by anorganism (which was sensitive before) due tothe use of an AMAs over a period of time.

This can happen with any microbe and is amajor clinical problem.

It depends on the microorganism as well as thedrug

Some bacteria are notorous for rapid acquisitionof resistance

Eg staphyloccoccui, coliforms, tubercle bacilli.

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Resistance may be developed by mutation or genetransfer.

Resistance once acquired it become prevalent due tothe selection pressure of a widely used AMAs.

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Resistant organism can be:-

Drug tolerant

Loss of affinity of the target biomolecule of the MO forAMA.

Acquisition of an alternative metabolic pathway Drug destroying

B- lactamase, CAF acetyl transfrase

Drugs impermeable Efflux pump

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Mechanisms of AMA resistance

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Cross resistance

Acquisition of resistance to one AMAs conferring

resistance to another AMA to which the organism has

not been exposed.

This is more commonly seen between chemically or

mechanistically related drugs,

Eg. Resistance to one sulfonamide means resistant to

all other.

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One Cause of resistance is misuse of theAMAs

1. Treatment of untreatable infection

2. Therapy of fever of undetermined origin.3. Improper dosage.

4. Improper reliance on chemotherapy alone.

5. Lack of adequate bacteriological information.

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To prevent or reduce bacterial resistance:-

Use antibiotic only when necessary.

Make sure that the indication, dose, and

duration of treatment are correct. Combine antibiotic when indicated.

Monitor pattern of resistance.

Limit the use of newest antibacterial.

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4. Super infection

This refer to the appearance of a new infection

as result of antimicrobial therapy

The use of most AMAs cause some alteration inthe normal microbial flora of the body

The normal flora contributes to host defense.

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5. Nutritional Deficiencies

Some of the B complex group of vitamins and

vit K synthesized by intestinal flora is utilized by

man

Prolonged use of AMA which alters the flora may result

in vit deficiency.

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6. Masking of an infection

A short course of AMA may be sufficient totreat one infection but only briefly suppressanother one contacted concurrently.

The infection will be masked masked initially,only manifest later in a sever form.

Single dose of Penicillin

Mask syphilis

Cure gonorrhea Short course Streptomycin

Mask TB

Cure trivial respiratory infection

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CLASSIFICATION OF ANTIMICROBIALS

Antimicrobial agents are classified based onchemical structure and proposedmechanism of action, as follows.

1. The Antimetabolites, Including trimethoprim and the sulfonamides, which

block essential enzymes of folate metabolism.

2. Agents that affect bacterial nucleic acidmetabolism, Rifamycins which inhibit RNA polymerase, and

The Quinolone, which inhibit topoisomerases;

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CLASSIFICATION OF ANTIMICROBIALS (CONT.)

3. Agents that inhibit synthesis ofbacterial cell wall. Including

The -lactam class (Penicillins, cephalosporins, and

carbapenems) and

Dissimilar agents such as cycloserine, vancomycin,and bacitracin

4. Agents that bind to the 30S ribosomal

subunit and alter protein synthesis,which generally are bactericidal. The aminoglycosides

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5. Agents that disrupt function of 30S or

50S ribosomal subunits to reversibly

inhibit protein synthesis, which

generally are bacteriostatic. Chloramphenicol, tetracyclines, erythromycin,

and clindamycin,

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6. Agents that act directly on the cell

membrane of the microorganism,

increasing permeability and leading to

leakage of intracellular compounds, Including

Detergents such aspolymyxin;

Polyene antifungal agents (e.g., nystatin

and amphotericin B)

which bind to cell-wall sterols; and the

lipopeptide.

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According to target MO affected they can be

classified as;-

1. Antibacterial

2. Antifungal

3. Antihelementics

4. Antiprotozoal

5. Anticancer

6. Antiviral

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According to antibacterial spectrum they

can be classified as:-

Narrow spectrum

Extended spectrum Gram +ve, and certain gram ve.

Wide spectrum Gram -ve, gram +ve, and certain bacterial

specious

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According to the type of action they can be

classified as:-

1. Bacteristatic agents:- that slow protein synthesis or

prevents microbial cell division.

2. Bactericidal agents:- that mediate complete killing of

the bacteria.

Generally bacteriostatic and bactericidal

combination is not advisable.

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Summary

.

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.

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Thank u

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CHEMOTHERAPY Introduction 1

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